Karel Kalecký, United States of America
Baylor Scott & White Research Institute Center of MetabolomicsAuthor Of 2 Presentations
METABOLOMIC AND LIPIDOMIC ANALYSIS IN ALZHEIMER’S AND PARKINSON’S DISEASE REVEALS SIMILARITIES AND DIFFERENCES IN PLASMA PROFILES INCLUDING ABNORMAL MICROBIAL METABOLITES
Abstract
Aims
Alzheimer’s (AD) and Parkinson’s disease (PD) are considered multifactorial in origin. In both, homeostasis of neurons is progressively impaired, leading to cellular death. Understanding metabolic changes can provide insight into processes affecting the cellular environment and disease etiology. We performed a metabolomic and lipidomic analysis in AD and PD, highlighting similarities and differences in their alterations.
Methods
Plasma samples were obtained from the Texas Alzheimer’s Research and Care Consortium (95 AD, 68 controls) and NINDS Parkinson's Disease Biomarkers Program (96 PD, 23 controls). Analysis of samples was performed on a Sciex QTrap 5500 UHPLC-MS/MS platform using the Biocrates MxP Quant 500 kit, which potentially detects 630 metabolites, including 523 lipid species, and calculates 232 metabolic indictors.
Results
We found 67 compounds and 41 indicators altered (FDR≤0.05) in AD, and 40 compounds and 28 indicators altered in PD. Multiple metabolites suggest microbiota involvement (AD: indole derivatives, TMAO, bile acids; PD: p-cresol sulfate; both: 7α-dehydroxylation of cholic acid, GDCA synthesis, 5-aminovalleric acid), reflecting unhealthy microbiome composition and increased toxin production. For example, elevated renal damage markers in PD (creatinine, SDMA) seem partially linked to the microbial urotoxin p-cresol sulfate (Pearson’s r=0.36, p<0.001). Other findings include changes in lipid metabolism indicative of elevated activity of phospholipase A2 and production of pro-inflammatory lipid species in both disorders.
Conclusions
AD and PD are associated with altered metabolic and lipid profiles in partial overlap. Our results implicate an altered gut microbial environment in both disorders. Microbiome remodeling to decrease bacteriotoxin load may be a suitable prophylactic and supportive treatment.
LIVE DISCUSSION
Presenter of 2 Presentations
LIVE DISCUSSION
METABOLOMIC AND LIPIDOMIC ANALYSIS IN ALZHEIMER’S AND PARKINSON’S DISEASE REVEALS SIMILARITIES AND DIFFERENCES IN PLASMA PROFILES INCLUDING ABNORMAL MICROBIAL METABOLITES
Abstract
Aims
Alzheimer’s (AD) and Parkinson’s disease (PD) are considered multifactorial in origin. In both, homeostasis of neurons is progressively impaired, leading to cellular death. Understanding metabolic changes can provide insight into processes affecting the cellular environment and disease etiology. We performed a metabolomic and lipidomic analysis in AD and PD, highlighting similarities and differences in their alterations.
Methods
Plasma samples were obtained from the Texas Alzheimer’s Research and Care Consortium (95 AD, 68 controls) and NINDS Parkinson's Disease Biomarkers Program (96 PD, 23 controls). Analysis of samples was performed on a Sciex QTrap 5500 UHPLC-MS/MS platform using the Biocrates MxP Quant 500 kit, which potentially detects 630 metabolites, including 523 lipid species, and calculates 232 metabolic indictors.
Results
We found 67 compounds and 41 indicators altered (FDR≤0.05) in AD, and 40 compounds and 28 indicators altered in PD. Multiple metabolites suggest microbiota involvement (AD: indole derivatives, TMAO, bile acids; PD: p-cresol sulfate; both: 7α-dehydroxylation of cholic acid, GDCA synthesis, 5-aminovalleric acid), reflecting unhealthy microbiome composition and increased toxin production. For example, elevated renal damage markers in PD (creatinine, SDMA) seem partially linked to the microbial urotoxin p-cresol sulfate (Pearson’s r=0.36, p<0.001). Other findings include changes in lipid metabolism indicative of elevated activity of phospholipase A2 and production of pro-inflammatory lipid species in both disorders.
Conclusions
AD and PD are associated with altered metabolic and lipid profiles in partial overlap. Our results implicate an altered gut microbial environment in both disorders. Microbiome remodeling to decrease bacteriotoxin load may be a suitable prophylactic and supportive treatment.